Role of the cellular prion protein in oligodendrocyte precursor cell proliferation and differentiation in the developing and adult mouse CNS

There are numerous studies describing the signaling mechanisms that mediate oligodendrocyte precursor cell (OPC) proliferation and differentiation, although the contribution of the cellular prion protein (PrPc) to this process remains unclear. PrPc is a glycosyl-phosphatidylinositol (GPI)-anchored glycoprotein involved in diverse cellular processes during the development and maturation of the mammalian central nervous system (CNS). Here we describe how PrPc influences oligodendrocyte proliferation in the developing and adult CNS. OPCs that lack PrPc proliferate more vigorously at the expense of a delay in differentiation, which correlates with changes in the expression of oligodendrocyte lineage markers. In addition, numerous NG2-positive cells were observed in cortical regions of adult PrPc knockout mice, although no significant changes in myelination can be seen, probably due to the death of surplus cells.

Sciatic and femoral nerve sensory neurones occupy different regions of the L4 dorsal root ganglion in the adult rat.

The topographical distribution of sciatic and femoral nerve sensory neuronal somata in the L4 dorsal root ganglion of the adult rat was mapped after retrograde tracing with one or two of the dyes Fast Blue, Fluoro-Gold, or Diamidino Yellow. The tracers were applied to the proximal transected end of either nerve alone, or from both nerves in the same animal using separate tracers. Three-dimensional reconstructions of the distribution of labelled neurones were made from serial sections of the L4 dorsal root ganglion which is the only ganglion that these two nerves share. The results showed that with little overlap, femoral nerve neurones distribute dorsally and rostrally whereas sciatic nerve neurones distribute medially and ventrally. This finding indicates the existence of a somatotopical organisation for the representation of different peripheral nerves in dorsal root ganglia of adult animals.

Effects of adult dysthyroidism on the morphology of hippocampal neurons.

This study investigates the effect of thyroid hormones on the morphology of hippocampal neurons in adult rats. Hypo- and hyperthyroidism were induced by adding 0.02% methimazole and 1% l-thyroxine, in drinking water from 40 days of age, respectively. When the rats were 89 days old their brains were removed and stained by a modified Golgi method and blood samples were collected in order to measure T4 serum levels. Neurons were selected and drawn using a camera lucida. Our results show that methimazole administration reduces the dendritic branching of the apical shafts of CA3 and CA1 pyramidal neurons mainly by increasing the distance to the first branch point in both types of neurons, and reducing branch points in the radius of 50 μm from the soma in CA1 neurons. Nevertheless, it was observed an increase of apical spine density in CA3 neurons from this group. Thyroxine reduces apical and basal tree of CA3 pyramidal neurons increasing the distance to the first branch point, reducing branch points in the radius of 50 μm from the soma and increases their apical and basal spine density. In CA1 field, thyroxine reduces the number of basal branch points. Both treatments seems to provoke alterations in the same direction reducing the dendritic branching and increasing spine density, although no significances appeared in some of the parameters analyzed. The effects are more evident in thyroxine than methimazole group; and in CA3 neurons than in CA1 neurons. In discussion it is pointed that the increase of spine density could be a mechanism to compensate the functionality reduction that can be provoke by the treatment effect on dendritic branching.

A comparison of three established age estimation methods on an adult Spanish sample.

Most current methods for adult skeletal age-at-death estimation are based on American samples comprising individuals of European and African ancestry. Our limited understanding of population variability hampers our efforts to apply these techniques to various skeletal populations around the world, especially in global forensic contexts. Further, documented skeletal samples are rare, limiting our ability to test our techniques. The objective of this paper is to test three pelvic macroscopic methods (1-Suchey-Brooks; 2- Lovejoy; 3- Buckberry and Chamberlain) on a documented modern Spanish sample. These methods were selected because they are popular among Spanish anthropologists and because they never have been tested in a Spanish sample. The study sample consists of 80 individuals (55 ♂ and 25 ♀) of known sex and age from the Valladolid collection. Results indicate that in all three methods, levels of bias and inaccuracy increase with age. The Lovejoy method performs poorly (27%) compared with Suchey-Brooks (71%) and Buckberry and Chamberlain (86%). However, the levels of correlation between phases and chronological ages are low and comparable in the three methods (< 0.395). The apparent accuracy of the Suchey-Brooks and Buckberry and Chamberlain methods is largely based on the broad width of the methods" estimated intervals. This study suggests that before systematic application of these three methodologies in Spanish populations, further statistical modeling and research into the co-variance of chronological age with morphological change is necessary. Future methods should be developed specific to various world populations, and should allow for both precision and flexibility in age estimation.

Multimorbidity patterns in a national representative sample of the Spanish adult population.

BACKGROUND: In the context of population aging, multimorbidity has emerged as a growing concern in public health. However, little is known about multimorbidity patterns and other issues surrounding chronic diseases. The aim of our study was to examine multimorbidity patterns, the relationship between physical and mental conditions and the distribution of multimorbidity in the Spanish adult population. METHODS: Data from this cross-sectional study was collected from the COURAGE study. A total of 4,583 participants from Spain were included, 3,625 aged over 50. An exploratory factor analysis was conducted to detect multimorbidity patterns in the population over 50 years of age. Crude and adjusted binary logistic regressions were performed to identify individual associations between physical and mental conditions. RESULTS: THREE MULTIMORBIDITY PATTERNS ROSE: 'cardio-respiratory' (angina, asthma, chronic lung disease), 'mental-arthritis' (arthritis, depression, anxiety) and the 'aggregated pattern' (angina, hypertension, stroke, diabetes, cataracts, edentulism, arthritis). After adjusting for covariates, asthma, chronic lung disease, arthritis and the number of physical conditions were associated with depression. Angina and the number of physical conditions were associated with a higher risk of anxiety. With regard to multimorbidity distribution, women over 65 years suffered from the highest rate of multimorbidity (67.3%). CONCLUSION: Multimorbidity prevalence occurs in a high percentage of the Spanish population, especially in the elderly. There are specific multimorbidity patterns and individual associations between physical and mental conditions, which bring new insights into the complexity of chronic patients. There is need to implement patient-centered care which involves these interactions rather than merely paying attention to individual diseases.

Mood and anxiety disorders across the adult lifespan: a European perspective

BACKGROUND: The World Mental Health Survey Initiative (WMHSI) has advanced our understanding of mental disorders by providing data suitable for analysis across many countries. However, these data have not yet been fully explored from a cross-national lifespan perspective. In particular, there is a shortage of research on the relationship between mood and anxiety disorders and age across countries. In this study we used multigroup methods to model the distribution of 12-month DSM-IV/CIDI mood and anxiety disorders across the adult lifespan in relation to determinants of mental health in 10 European Union (EU) countries. METHOD: Logistic regression was used to model the odds of any mood or any anxiety disorder as a function of age, gender, marital status, urbanicity and employment using a multigroup approach (n = 35500). This allowed for the testing of specific lifespan hypotheses across participating countries. RESULTS: No simple geographical pattern exists with which to describe the relationship between 12-month prevalence of mood and anxiety disorders and age. Of the adults sampled, very few aged ≥ 80 years met DSM-IV diagnostic criteria for these disorders. The associations between these disorders and key sociodemographic variables were relatively homogeneous across countries after adjusting for age. CONCLUSIONS: Further research is required to confirm that there are indeed stages in the lifespan where the reported prevalence of mental disorders is low, such as among younger adults in the East and older adults in the West. This project illustrates the difficulties in conducting research among different age groups simultaneously.

Characterization of nontypable haemophilus influenzae isolates recovered from adult patients with underlying chronic lung disease reveals genotypic and phenotypic traits associated with persistent infection

Nontypable Haemophilus influenzae (NTHi) has emerged as an important opportunistic pathogen causing infection in adults suffering obstructive lung diseases. Existing evidence associates chronic infection by NTHi to the progression of the chronic respiratory disease, but specific features of NTHi associated with persistence have not been comprehensively addressed. To provide clues about adaptive strategies adopted by NTHi during persistent infection, we compared sequential persistent isolates with newly acquired isolates in sputa from six patients with chronic obstructive lung disease. Pulse field gel electrophoresis (PFGE) identified three patients with consecutive persistent strains and three with new strains. Phenotypic characterisation included infection of respiratory epithelial cells, bacterial self-aggregation, biofilm formation and resistance to antimicrobial peptides (AMP). Persistent isolates differed from new strains in showing low epithelial adhesion and inability to form biofilms when grown under continuous-flow culture conditions in microfermenters. Self-aggregation clustered the strains by patient, not by persistence. Increasing resistance to AMPs was observed for each series of persistent isolates; this was not associated with lipooligosaccharide decoration with phosphorylcholine or with lipid A acylation. Variation was further analyzed for the series of three persistent isolates recovered from patient 1. These isolates displayed comparable growth rate, natural transformation frequency and murine pulmonary infection. Genome sequencing of these three isolates revealed sequential acquisition of single-nucleotide variants in the AMP permease sapC, the heme acquisition systems hgpB, hgpC, hup and hxuC, the 3-deoxy-D-manno-octulosonic acid kinase kdkA, the long-chain fatty acid transporter ompP1, and the phosphoribosylamine glycine ligase purD. Collectively, we frame a range of pathogenic traits and a repertoire of genetic variants in the context of persistent infection by NTHi.